There have been reported various methods for producing optically active alcohols using metal complexes as a catalyst. In particular, a method for synthesizing optically active alcohols from ketone compounds by a reductive process using a ruthenium complex as a catalyst in the presence of a base has been intensively researched.
With respect to asymmetric hydrogenation and a catalyst for producing optically active alcohols by asymmetric hydrogenation of ketones using hydrogen as a reducing agent, for example, Japanese Unexamined Patent Application Publication No. 8-225466 has reported an example in which an optically active alcohol was produced by hydrogenation of a ketone compound in the presence of a base, using a mixture of a complex, in which BINAP (2,2′-bis(diphenylphosphine)-1,1′-binaphthyl) and DMF coordinate to ruthenium, and diphenylethylenediamine as a catalyst.
However, a hydrogenation reaction does not efficiently proceed or an enantiomer excess may be insufficient depending on the structure of the ketone compound used. In the above-described catalyst system, a ketone compound unstable to a base and a ketone having acidic hydrogen cannot be hydrogenated because the reaction is effected under basic conditions. In order to solve this problem, some attempts have been made.
For example, Japanese Unexamined Patent Application Publication No. 2003-104993 has reported some examples in each of which an optically active alcohol was produced by hydrogenation of a ketone compound unstable to a base using as a catalyst tetrahydroborate salt of a chiral ruthenium metal complex containing a diphosphine compound, such as BINAP, and a diamine compound, which coordinate to ruthenium, in 2-propanol not containing a base under pressurized hydrogen. Specifically, ethyl 4-acetylbenzoate and 3-nonen-2-one are used for producing respective corresponding optically active alcohols.
However, the catalyst described in Japanese Unexamined Patent Application Publication No. 2003-104993 may exhibit low yield and low enantiomer excess depending on the reaction substrate used, and thus the structures of applicable ketone compounds are limited.
For catalytic asymmetric hydrogenation, many methods using an alcohol or formic acid as a reducing agent, i.e., catalytic asymmetric reduction reactions, have been reported. In particular, a chiral ruthenium catalyst (Japanese Unexamined Patent Application Publication No. 11-322649) having an amine ligand containing a sulfonylamide group as an anchor has noteworthy performance. There have been also reported similar catalyst systems (Chem. Commun. 1996, 223. Organometallics 1996, 15, 1087) each having a ruthenium-amine complex as a basic skeleton. Also, rhodium and iridium catalysts (J. Org. Chem. 1999, 64, 2186) each having a metal-amine bond have been reported. These chiral metal catalysts can asymmetrically reduce many kinds of ketone substrates as compared with the above-described hydrogenation catalysts. However, the activation ability of hydrogen is low, and only organic compounds such as 2-propanol and formic acid can be used as hydrogen sources. Therefore, the catalyst must be used in a larger amount than that for asymmetric hydrogenation with hydrogen. In addition, the use of formic acid has the problem of corrosion of a reaction kettle. Further, there has been reported asymmetric reduction of phenacyl chloride using formic acid as a reducing agent in the presence of a catalyst containing rhodium as a central metal. This reduction also has problems with catalytic activity and the use of corrosive formic acid. Therefore, there has been demand for asymmetric hydrogenation of various ketone substrates using hydrogen as a reducing agent with high enantio-selectivity and high efficiency.